The Biologic Role of Vitamin D in Neurometabolic Conditions

Keith Van Haren, MD, an assistant professor of neurology at Stanford University

Keith Van Haren, MD

Research has linked an individual patient’s vitamin D status to a curiously wide range of disease states, but investigators have suggested that the confusion surrounding these ostensible associations could be partially due to the pre‐existing expectations the physiologic roles that vitamin D plays.

Recently, Keith Van Haren, MD, an assistant professor of neurology at Stanford University who specializes in child neurology, and colleagues, conducted an unbiased characterization of vitamin D's in vivo effects on human immune cells in states of both health and disease. Ultimately, they found that vitamin D plays an unexpectedly prominent role in fuel dependency, energy efficiency, and cell survival within the human immune system.¹

They suggested that these findings “offer new vantage points for understanding vitamin D's role in human health and disease” particularly focused on disorders of fatty acid metabolism, such as X‐linked adrenoleukodystrophy (ALD), a rare, genetic disorder characterized by the breakdown or loss of myelin. To find out more about the findings, NeurologyLive spoke with Van Haren in an interview.

You recently conducted work on Vitamin D’s biologic role in patients with multiple sclerosis, could you provide insight into that?

Keith Van Haren, MD: I presented on our investigation into the human and transcriptome for vitamin D [at the Child Neurology Society’s annual meeting], where we analyzed 2 human transcriptomes from clinical trials of vitamin D supplementation. We had a specific intent in mind, trying to look at some of the underappreciated potential metabolic effects of vitamin D biology. We were coming from an experience of finding a vitamin D signal as a risk factor for one of our metabolic disorders, called X‐linked A. We found that really interesting, but inexplicable. There's no way to explain that finding in the context of our current knowledge of vitamin D’s biology, so we thought we should see what vitamin D might be doing in another population.

We began by looking at the effects of vitamin D in the transcriptomes of MS patients who were supplementing vitamin D as part of a clinical trial. We found much more than we expected. It was very similar and pretty much in line with what we were thinking: a lot of fatty acid metabolism—just vastly more than we imagined. Then, we thought these are really interesting signals, is this unique to MS, or is it something else? So, we validated it in a second population of non-MS patients, in a European study of vitamin D supplementation to prevent adults at risk of diabetes from going on to develop diabetes. We found the same signals, actually, with a few exceptions, and the story we built was sort of derived around this data.

Were there any specific findings you thought were particularly interesting or unexpected?

There were a few key, big-picture things that fell out. One was that vitamin D seemed to be regulating metabolism as kind of its first order effect. We saw a decrease in fatty acid metabolism, an increase in glucose metabolism, and an increase in cell survival. And unexpectedly, a kind of a decrease in mitochondrial metabolism and what looks like heat production. As we were looking at these kinds of big-picture phenomenon, we thought that this looked a lot like hibernation physiology. Low vitamin D states look like the kind of physiology a bear might want, where you produce more heat and you consume more fats. It so happens that that exactly coincides with the cycles that vitamin D runs through over the course of a year if you live at any major latitude where there's more sun in the summer, which means you get more vitamin D through ultraviolet exposure, and in the wintertime, you'll drop substantially.

With that, means is that in summertime you'd be prime for glucose and carbohydrate metabolism, or lower heat production, and in the wintertime, you'd be primed for just the opposite. So, sort of out fell kind of a new idea for what vitamin D you might be doing. If you take an even further step back, you can see that vitamin D could serve as actually this interesting geolocator for organisms who are trying to gain any survival advantage as they evolve and migrate around the globe. At more extreme latitudes, the available energy is much different—you have less sun, less heat, and because you have less sun, you have fewer carbohydrates and plants. The organism needs to be primed for a different environment and vice-versa as you move further south, so you have more heat, more sun, more plants/carbohydrates.

One can see, although there's no way to prove this from our data set, that it suggests that vitamin D could potentially have served as a function of a hormone the organism to provide it a sense of where it is in the map, what energy needs it might need to anticipate, and how it needs to basically synchronize itself with its anticipated environmental resources.

REFERENCE

1. Van Haren K. Monocyte, T‐cell, and B‐cell Transcriptomes from Multiple Sclerosis Patients Treated with Vitamin D Highlight Metabolic Pathways Relevant to Immune Regulation. Presented at: Child Neurology Society annual meeting: Chicago, IL; October 15 to 18, 2018. childneurologysociety.org/docs/default-source/2018-cns/platform-presentations-2018.pdf. Accessed February 13, 2019.